| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 10018 |
Name | BCL2L11 |
Synonymous | BCL2-like 11 (apoptosis facilitator);BCL2L11;BCL2-like 11 (apoptosis facilitator) |
Definition | bcl-2 interacting mediator of cell death|bcl-2 interacting protein Bim|bcl-2-like protein 11|bcl-2-related ovarian death agonist |
Position | 2q13 |
Gene type | protein-coding |
Title | Abstract |
| DNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis. | In the autoimmune syndrome rheumatoid arthritis (RA), T cells and T-cell precursors have age-inappropriate shortening of telomeres and accumulate deoxyribonucleic acid (DNA) double strand breaks. Whether damaged DNA elicits DNA repair activity and how this affects T-cell function and survival is unknown. Here, we report that naive and resting T cells from RA patients are susceptible to undergo apoptosis. In such T cells, unrepaired DNA stimulates a p53-ataxia telangiectasia mutated-independent pathway involving the non-homologous-end-joining protein DNA-protein kinase catalytic subunit (DNA-PKcs). Upregulation of DNA-PKcs transcription, protein expression and phosphorylation in RA T cells co-occurs with diminished expression of the Ku70/80 heterodimer, limiting DNA repair capacity. Inhibition of DNA-PKcs kinase activity or gene silencing of DNA-PKcs protects RA T cells from apoptosis. DNA-PKcs induces T-cell death by activating the JNK pathway and upregulating the apoptogenic BH3-only proteins Bim and Bmf. In essence, in RA, the DNA-PKcs-JNK-Bim/Bmf axis transmits genotoxic stress into shortened survival of naive resting T cells, imposing chronic proliferative turnover of the immune system and premature immunosenescence. Therapeutic blockade of the DNA-PK-dependent cell-death machinery may rejuvenate the immune system in RA. |